Breakthrough Invasive Mold Infections Under Posaconazole Prophylaxis (BIMI)

NCT04720144 | Unknown

• 1 other identifier: 2020-01719
• Study Type: observational
• Target: 300
• Locations: 3 countries
• Sites: 8

Brief Summary

Invasive mold infections (IMI) mainly affect patients with hematologic malignancies receiving intensive chemotherapy or after hematopoietic stem cell transplantation (HSCT). Prolonged neutropenia after remission induction chemotherapy (\>10 days duration) and continuous immunosuppression in the context of prevention or therapy of graft versus host disease (GVHD) for HSCT recipients (first 100 days post-transplantation and thereafter if GVHD is present) are considered as periods at high risk of IMI. Posaconazole prophylaxis is prescribed according to current guidelines to reduce the occurrence of IMI. Nevertheless, breakthrough IMI (bIMI), i.e. IMI occurring under mold-active prophylaxis, are still observed. The investigators hypothesized that the epidemiology of bIMI (under posaconazole prophylaxis) differs from that of IMI occurring in the absence of mold-active antifungal prophylaxis. Because bIMI are rare events since the introduction of posaconazole prophylaxis, epidemiological data of bIMI are scarce. This study aims to i) describe the epidemiology, clinical features, treatment and outcome of bIMI, ii) assess the causes of bIMI, iii) determine potential risk factors associated with the developllement of bIMI iv) assess the impact of bIMI on overall mortality. Design Retrospective and prospective, observational, case-control, multicenter, international study. The retrospective part will enroll previously identified bIMI cases and control cases (1:2) over the last five years: October 1st 2015 to September 30st 2020. The prospective part will enroll bIMI cases and control cases (1:2) occurring over a two-year period: October 1st 2020 to September 30st 2022. Setting The aim is to enroll 10 to 15 European centers with dedicated units for hematologic cancer patients. Currently, six centers have confirmed their participation (from Switzerland and Germany). Study Population Adult (≥ 18 years old) patients with a hematologic malignancy receiving posaconazole prophylaxis during induction, consolidation or re-induction chemotherapy or after HSCT. Cases : patients receiving posaconazole prophylaxis for at least 7 days and diagnosed with bIMI proven or probable according to EORTC-MSGERC. Controls: patients receiving posaconazole prophylaxis for at least 7 days, without diagnosis of bIMI possible, probable or proven according to EORTC-MSGERC. The objective is to enroll about 100 bIMI cases and 200 controls.

Conditions

Invasive Mold Infections; Breakthrough Invasive Mold Infections; Hematologic Malignancy; Hematologic Diseases

Keywords

Posaconazole; Antifungal prophylaxis

Outcome Measures

Primary Outcomes (2)

• Epidemiological description of bIMI

  * Assessment of the cause of bIMI (intrinsically resistant mold pathogen vs susceptible mold pathogen but insufficient posaconazole serum concentration vs unknown) * Description of clinical features, treatment and outcome of bIMI

  At inclusion

• Assessment of the risk factors of bIMI

  • Univariate and multivariate analyses of the parameters associated with an increased risk of bIMI (in particular, the association of a threshold of posaconazole concentration and bIMI) by comparison of bIMI cases with controls (posaconazole prophylaxis and no bIMI)

  At inclusion

Secondary Outcomes (2)

• Assessment of the impact of bIMI on overall mortality

  6 weeks and 12 weeks after inclusion

• Assessment of factors influencing outcomes of bIMI

  6 weeks and 12 weeks after inclusion

Study Arms (2)

bIMI cases

Adult (≥ 18 years old) patients with a hematologic malignancy receiving posaconazole prophylaxis (oral tablets or IV administration) for: i) Induction, consolidation or re-induction chemotherapy for acute leukemia or myelodysplastic syndrome (i.e. expected duration of neutropenia post-chemotherapy of ≥ 10 days) OR ii) Allogeneic hematopoietic stem cell transplant recipients during the post-transplantation phase (100-day post-transplantation) or later in case of intensified immunosuppression for moderate to severe graft vs host disease (GVHD). AND iii) Being diagnosed with proven or probable bIMI according to the EORTC-MSGERC classification (10) while on continuous posaconazole prophylaxis for at least 7 days.

Controls

For each bIMI case, we will include 2 control cases fulfilling the following criteria: i) Receiving continuous posaconazole prophylaxis for at least 7 days ii) No diagnosis of proven, probable or possible IMI according to EORTC-MSGERC classification (10) during the entire hospital stay

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adults diagnosed with hematologic malignancies under posaconazole prophylaxis for one of the above mentionned reasons.

You may qualify if:

• Cases:
• Adult (≥ 18 years old) patients with a hematologic malignancy receiving posaconazole prophylaxis (oral tablets or IV administration) for:
• i) Induction, consolidation or re-induction chemotherapy for acute leukemia or myelodysplastic syndrome (i.e. expected duration of neutropenia post-chemotherapy of ≥ 10 days)
• ii) Allogeneic hematopoietic stem cell transplant recipients during the post-transplantation phase (100-day post-transplantation) or later in case of intensified immunosuppression for moderate to severe graft vs host disease (GVHD).
• AND
• iii) Being diagnosed with proven or probable bIMI according to the EORTC-MSG classification (10) while on continuous posaconazole prophylaxis for at least 7 days.
• Controls:
• For each bIMI case, we will include 2 control cases fulfilling the following criteria:
• i) Receiving continuous posaconazole prophylaxis for at least 7 days
• ii) No diagnosis of proven, probable or possible IMI according to EORTC-MSG classification (10) during the entire hospital stay.
• And matched to bIMI cases according to the following criteria:
• iii) Hospitalization in the same ward within the same year (+/- 12 months interval)
• iv) Same underlying condition related to hematologc cancer: a) HSCT within 100 days post-engraftment, b) HSCT \> 100 days post-engraftment with intensified immunosuppressive regimen for severe GVHD, c) induction chemotherapy for acute myeloid or lymphoid leukemia, or myelodysplastic syndrome, d) other hematologic disorders (e.g. aplastic anemia) with prolonged neutropenia and/or immunosuppressive regimen.

You may not qualify if:

• Patients with a diagnosis of possible IMI according to the EORTC-MSG classification.
• Patients with a positive fungal biomarker in serum (e.g. galactomannan or beta-glucan) in the absence of clinical or radiological criteria of IMI according to the EORTC-MSG classification.

Sponsors & Collaborators

• Centre Hospitalier Universitaire Vaudois: lead

Study Sites (8)

Medical University of Innsbruck

Innsbruck, Austria

NOT YET RECRUITING

University Hospital Cologne

Cologne, Germany

NOT YET RECRUITING

Universitätsspital Basel

Basel, Switzerland

RECRUITING

Inselspital Bern

Bern, Switzerland

RECRUITING

Hôpital Cantonal de Fribourg

Fribourg, Switzerland

RECRUITING

Hôpitaux Universitaires de Genève (HUG)

Geneva, Switzerland

RECRUITING

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, Switzerland

RECRUITING

Kantonsspital St.Gallen

Sankt Gallen, Switzerland

NOT YET RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms; Hematologic Diseases

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hemic and Lymphatic Diseases

Study Officials

• Frederic Lamoth

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Frederic Lamoth

CONTACT

+41213141111; frederic.lamoth@chuv.ch

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: January 22, 2021
• Study Start: October 1, 2020
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: February 9, 2021

Record last verified: 2021-02

Locations

DE (1); AU (1); CH (6)